Manufacture of n.n&#39;-diacyl-compounds of ethylene-diamine and its derivatives



Patented Sept. 5, 1933 ATENT GFFlCE M A N U F A C T U R E OF N.N'DIACYLCOM POUNDS F ETHYLENE-DIAMINE AND ITS DEREVATIVES Karl Wilhelm Eosenmund, Kiel, Germany No Drawing. Application June 19, 1931, Serial No. 545,619, and in Germany October 31, 1929 16 Claims.

This application has been filed in Germany on October 31, 1929.

This invention has reference to the manufacture of acyl-compounds of diamines, and more particularly to the acyl-compounds of ethylene diamine and its derivatives, and it is intended to facilitate the manufacture of such products, and thereby to also increase the number of products of this class. Acyl-compounds of ethylene-diamine having indentical acyl-radicals in the two amino-groups have been frequently obtained heretofore, but as far as I am aware, it has not been possible heretofore to manufacture aoylcompounds of the ethylene-diamine with different acyl-radicals.

In accordance with my invention the diacylcompounds may be obtained by starting with the monoacyl-compounds of ethylene-diamine 01' with the N-alkylated ethylene-diamine with secondary amino-group and introducing into these compounds by methods otherwise known another acyl group of a monobasic carboxylic acid. The process is carried out in accordance with the following formula:-

in which RC0 and RICO represent acyl groups, as for instance, acetyl, di-ethyl-acetyl-bromine with the formula and like compounds.

The introduction of the acyl-radicals may be carried out with all acyl-residues of monobasic acids which may be used as chlorides, as the acids themselves or their anhydrides or esters. It has been shown by quantitative analysis of the elements present and by the fact that the products fail to possess basic properties that by this introduction into the monoaoyl-ethylene-diamines the N.N' diacyl-amines mentioned in the formula are actually obtained. The mixed diacyl-compounds obtained are of great therapeutic value on account of their physiological properties.

In its generic form my invention can be described as a process of forming mixed l T:N diacyl substituted compounds of ethylene diamine by reacting together at various temperatures a compound having the generic formula with a compound having the generic formula B-COX. This reaction produces the new compounds of my invention which can be represented by the generic formula being mixed NzN diacyl substituted compounds of ethylene diamine or of N-alkylated ethylene diamines. In the above formula K and K1 represent hydrogen or alkyl groups, RCO--X represents a monobasic carboxylic acid or the acid halide, the anhyclride or the ester of such an acid, while RCO and R1CO- represent the acyl groups of different monobasic carboxylic acids.

The invention will be more fully explained by reference to the following examples, viz:-

(1) l0 monoacetyl-ethy1ene-diamine are dissolved in 20 grams water and are treated with somewhat more than the calculated amount of bromine-diethyl-acetyl-bromide having the formula GHaOONHOHZCHENHGO llBr is partly precipitated as an oil, and it partly remains in the solution. The compound solidifies after being allowed to stand for some length of time, and after having been crystallized from ligroin, it has a melting point of 72 C. The yield is 70%.

(2) Propionyl-ethylene-diamine,

NH2CH2CH2NHCOC2H5, and bromine-isovaleryl-br0mide,

(3E3 HGBrGHOOBr CH3 are caused to react upon each other in molecular quantities. The propionyl-bromine-isovalerylethylene-diamine 9 H$B1'OHOONHOH2OH2NHCOCzHs,

formed meltsat 193 C., and the propionyl-cromine-diethyl-acetyl-ethylene-diamine CH: GHzOHzCONHCHzCHzNHOOCHBr-J-AT has the melting point 57-59 C. The yield is 32 (3) Acetyl-salicoyl-ethylene-diamine OH O! omcomzromonmno-O is obtained with a yield of 60%.

(4) Acetyl-benzoyl-ethyleneediamine, having the formula is obtained as follows:1.3 moles of acetylethylene-diamine and 1 mole of benzoic acid are heated to 180 C. The resultant mixture is then treated with bicarbonate of soda and the residue obtained is crystallized from ethyl acetate in the form of white needles, melting at 175 C. It constitutes the desired diacyl product. The yield is 85%.

(5) Bromine-diethyl-acetyl-cyclohexyl -acetyl- Y ethylene-diamine v CHgCONHCHzCHzN is obtained as follows:-10-grams acetyl-cyclo hexyl-ethylene-diamine CsH11NH.CHzCHz-NH.COCH3 (boiling point at 2.5 mm. pressure USS-173 C.)

manufactured by the catalytic reduction of a 7 mixture of molecular quantities of acetyl ethylene-diamirie and cyclo-hexanone in accordance with the following formula viz.:

' are shaken with the calculated amount of bromine-diethyl-acetyl-chloride C 2H5 1 BrC-OOCl CzHli in a soda-alkaline menstruum, which causesthe compound to separate out. The yield is 13 grams. The compound crystallizes from alcohol and has a melting point 104 C. I V

(6) Acetyl-cinnamoyl-ethylene-diamine.

The residue is is obtained as followsz-lO grams propionylethylene-diamine are shaken with the calculated amount of cinnamyl-chlorid while keeping the mixture cooled. The new compound crystallizes from ethyl acetate in white needles; melting point 183 C. Yield 85%.

It should be understood that the invention is not confined to the examples herein given merely by way of illustration, nor to the quantities and mode of operation stated, except as otherwise appears from the appended claims.

The monoacyl-compounds may for instance be obtained in accordance with my co-pending application, relating to their manufacture, and bearing Serial No. 545,620, filed June 19, 1931.

I claim:-

1. N.N-diacyl compounds of diamines having the generic'formula RCONHCH2CH2NHCOR1 in which RC0 and. R100 represent different acyl groups.

2. Acetyl-salicoyl-ethylene-diamine,

GHaGONHOHzCHzNHC- having a melting point of 140-141 C. a

3. Bromine diethyl acetyl-cyclohexyl-acetylethylene-diamine,

crystallizable from alcohol andpossessing fluidity point 104 C. V

4. Propionyl bromine isovaleryl-ethylene-diamine, I

crystallizable from ethyl acetate and having a.

melting point of 193 C.

5. In the manufacture of mixed N:N diacyl substituted compounds of ethylene diamine, the I process which comprises reacting together, at temperatures ranging from about room tempera-' tures to about 180 C., a compound represented by the generic formula with a compound having the generic formula RCO -X, until a solid compound is formed,

then recovering the solid so formed; 13-00- and R1-CO in the above formulae representing the acyl groups of different monobasic carboxylic acids, K and K1 representing hydrogen or alkyl groups and R--CO-.X representing a monobasic carboxylic acid'or the acid halide, the anhydride 4 or the ester of such an acid.

I 6. The process of cla-im 5 wherein R-COX represents an acidhalide of a monobasic carboxylic acid.

7. The processor claim SwhereinR-CO-X 13. The process of claim 5 wherein K and K1 represent hydrogen and RCOX represents the ester of a monobasic carboxylic acid.

14. The process of claim 5 wherein the reaction is conducted in an alkaline medium.

15. Mixed N:N diacyl substituted ethylene diamines having the generic formula R-CONKCHzCHz-NK1-COR1 wherein RCO and R1CO- represent acyl groups of different monobasic carboxylic acids and K and K1 represent hydrogen or alkyl groups. 16. The products of claim 15 wherein at least one of K and K1 represents an alkyl group.

KARL WILHELM ROSENMUND. 

